Our approach to gene silencing at Silence Therapeutics

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What specific technology is Silence Therapeutics using?

Delivery is key to the success of gene silencing. In order to be effective, siRNA must be efficiently transported to the cells of the target tissues. However, the human body is incredibly complex and delivering gene silencing medicine to precisely the right cells is a significant challenge. This is particularly difficult when targeting the brain and the liver.

Silence Therapeutics has developed an effective delivery platform. Our approach is to combine medicines with chemical ‘address tags’ that deliver RNAi to the right cell in the right part of the body. This allows for a highly targeted and precise approach.

In the case of liver cells, we combine our RNAi molecules with a naturally occurring sugar called GaINAc (the short name for N-Acetylgalactosamine), which is found in high quantities in the liver cells. This allows the RNAi molecules to be transported directly into the liver cells so that they can achieve their purpose.

Silence Therapeutics has also developed a ‘linker’ which makes it possible to attach the GalNAc sugar to our siRNA molecules.

Our specific approach is called the mRNAi GOLD Platform.

We are also investigating other potential delivery platforms to target genes expressed in other parts of the body, not just the liver.

+ What are the benefits of the RNAi–based approach used by Silence Therapeutics?

RNAi uses a gene’s own DNA sequence to turn it off and stop its effects, or ‘silence’ it, temporarily. Silence Therapeutics RNAi-based therapies use a very tailored and precise approach to target specific genes in specific parts of the body, for example the liver. This means that the effects are more potent and predictable. In turn, these RNAi-based therapies are likely to be more effective than traditional approaches. Therefore, they have a greater chance of clinical trial success and drug approval than the industry average. This means new medicines can be provided more quickly to those that can benefit from them.

Also, the effect of gene silencing is temporary. It does not cause permanent changes to DNA (unlike gene therapy). If any unwanted effects are produced, they are only temporary and they resolve once the medicine has been naturally broken down in the body.

+ Are there any other benefits for patients?

GalNAc-siRNA conjugates (which are medicines combining siRNA molecules with the GalNAc delivery system) can be administered ‘subcutaneously’ (via a standard injection underneath the skin), rather than via intravenous infusion (via a drip directly into a vein). This enables patients to administer the treatment themselves at home and reduces the need for hospital visits.

The effects are long-lasting: genes may be ‘silenced’ for more than two months after a single injection, again reducing the burden of treatment on patients.

The targeted delivery - to the right cells in the right part of the body – means that most potential side effects can be anticipated. In contrast, traditional medicines are less specific as they can affect many different cell types, so ‘off-target’ side effects can be more likely and challenging to predict. Furthermore, as our medicines do not cause permanent changes to DNA, any unwanted effects are only temporary.

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